Abstract：
BACKGROUND: Maple syrup urine disease (MSUD) is a rare disease for which newborn screening (NBS) is feasible but not universally applied in China. We shared our experiences with MSUD NBS.
METHODS: Tandem mass spectrometry-based NBS for MSUD was implemented in January 2003, and diagnostic methods included urine organic acid analysis via gas chromatography-mass spectrometry and genetic analysis.
RESULTS: Six MSUD patients were identified from 1.3 million newborns, yielding an incidence of 1:219,472, in Shanghai, China. The areas under the curve (AUCs) of total leucine (Xle), Xle/phenylalanine ratio, and Xle/alanine ratio were all 1.000. Some amino acid and acylcarnitine concentrations were markedly low in MSUD patients. 47 MSUD patients identified here and in other centers were investigated, which included 14 patients identified by NBS and 33 patients diagnosed clinically. Forty-four patients were subclassified into classic (n = 29), intermediate (n = 11) and intermittent (n = 4) subtypes. Due to earlier diagnosis and treatment, screened classic patients showed a higher survival rate (62.5%, 5/8) than clinically diagnosed classic patients (5.2%, 1/19). Overall, 56.8% (25/44) of MSUD patients and 77.8% (21/27) of classic patients carried variants in the BCKDHB gene. Among 61 identified genetic variants, 16 novel variants were identified.
CONCLUSIONS: MSUD NBS in Shanghai, China, enabled earlier detection and increased survivorship in the screened population.
METHODS: Tandem mass spectrometry-based NBS for MSUD was implemented in January 2003, and diagnostic methods included urine organic acid analysis via gas chromatography-mass spectrometry and genetic analysis.
RESULTS: Six MSUD patients were identified from 1.3 million newborns, yielding an incidence of 1:219,472, in Shanghai, China. The areas under the curve (AUCs) of total leucine (Xle), Xle/phenylalanine ratio, and Xle/alanine ratio were all 1.000. Some amino acid and acylcarnitine concentrations were markedly low in MSUD patients. 47 MSUD patients identified here and in other centers were investigated, which included 14 patients identified by NBS and 33 patients diagnosed clinically. Forty-four patients were subclassified into classic (n = 29), intermediate (n = 11) and intermittent (n = 4) subtypes. Due to earlier diagnosis and treatment, screened classic patients showed a higher survival rate (62.5%, 5/8) than clinically diagnosed classic patients (5.2%, 1/19). Overall, 56.8% (25/44) of MSUD patients and 77.8% (21/27) of classic patients carried variants in the BCKDHB gene. Among 61 identified genetic variants, 16 novel variants were identified.
CONCLUSIONS: MSUD NBS in Shanghai, China, enabled earlier detection and increased survivorship in the screened population.
摘要：
背景：枫糖浆尿病（MSUD）是一种罕见的疾病，新生儿筛查（NBS）是可行的，但在中国并未普遍应用。我们与MSUDNBS分享了我们的经验。
方法：MSUD的基于串联质谱的NBS于2003年1月实施，诊断方法包括通过气相色谱-质谱和遗传分析进行尿液有机酸分析。
结果：从130万新生儿中发现了6名MSUD患者，在上海，发病率为1:219,472，中国。总亮氨酸（Xle）的曲线下面积（AUCs），XLE/苯丙氨酸比，Xle/丙氨酸比值均为1.000。MSUD患者的某些氨基酸和酰基肉碱浓度明显较低。对此处和其他中心确定的47名MSUD患者进行了调查，其中包括由NBS确定的14例患者和临床诊断的33例患者。44例患者被细分为经典(n=29)，中间（n=11）和间歇性（n=4）亚型。由于早期的诊断和治疗，经筛选的经典患者生存率较高(62.5%，5/8）比临床诊断的经典患者（5.2%，1/19）。总的来说,56.8％（25/44）的MSUD患者和77.8％（21/27）的经典患者携带BCKDHB基因变异。在61个确定的遗传变异中，鉴定出16个新的变体。
结论：MSUDNBS在上海，中国,能够在筛查人群中更早地检测并增加存活率。
方法：MSUD的基于串联质谱的NBS于2003年1月实施，诊断方法包括通过气相色谱-质谱和遗传分析进行尿液有机酸分析。
结果：从130万新生儿中发现了6名MSUD患者，在上海，发病率为1:219,472，中国。总亮氨酸（Xle）的曲线下面积（AUCs），XLE/苯丙氨酸比，Xle/丙氨酸比值均为1.000。MSUD患者的某些氨基酸和酰基肉碱浓度明显较低。对此处和其他中心确定的47名MSUD患者进行了调查，其中包括由NBS确定的14例患者和临床诊断的33例患者。44例患者被细分为经典(n=29)，中间（n=11）和间歇性（n=4）亚型。由于早期的诊断和治疗，经筛选的经典患者生存率较高(62.5%，5/8）比临床诊断的经典患者（5.2%，1/19）。总的来说,56.8％（25/44）的MSUD患者和77.8％（21/27）的经典患者携带BCKDHB基因变异。在61个确定的遗传变异中，鉴定出16个新的变体。
结论：MSUDNBS在上海，中国,能够在筛查人群中更早地检测并增加存活率。
